Li Zhang1, Ge Lin, Qi Chang, Zhong Zuo. 1. School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.
Abstract
PURPOSE: The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process. METHODS: The intestinal absorption of B was characterized using Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model. In addition, preliminary metabolic kinetics of B was evaluated in both rat and human intestinal S9 fractions. RESULTS: B was well absorbed and extensively metabolized to baicalin (BG), baicalein-7-O-beta-glucuronide, in rat intestinal perfusion model, whereas less extent of metabolism was observed in the Caco-2 cell monolayer model. Moreover, BG generated in the intestinal epithelium during the absorption of B also rapidly transported to both the apical side (the apical chamber of Caco-2 model and the perfusate of the intestinal perfusion model) as well as the basolateral side of the small intestine (the basal chamber of Caco-2 model and the mesenteric vein of the intestinal perfusion model). From the preliminary metabolic studies, it was found that a higher loading dose of B resulted in a less extent of metabolism in intestine. In addition, the extent of metabolism of B was similar in jejunum and ileum when 50 microM of B was perfused through different sections of rat small intestine. CONCLUSION: The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.
PURPOSE: The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process. METHODS: The intestinal absorption of B was characterized using Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model. In addition, preliminary metabolic kinetics of B was evaluated in both rat and human intestinal S9 fractions. RESULTS: B was well absorbed and extensively metabolized to baicalin (BG), baicalein-7-O-beta-glucuronide, in rat intestinal perfusion model, whereas less extent of metabolism was observed in the Caco-2 cell monolayer model. Moreover, BG generated in the intestinal epithelium during the absorption of B also rapidly transported to both the apical side (the apical chamber of Caco-2 model and the perfusate of the intestinal perfusion model) as well as the basolateral side of the small intestine (the basal chamber of Caco-2 model and the mesenteric vein of the intestinal perfusion model). From the preliminary metabolic studies, it was found that a higher loading dose of B resulted in a less extent of metabolism in intestine. In addition, the extent of metabolism of B was similar in jejunum and ileum when 50 microM of B was perfused through different sections of rat small intestine. CONCLUSION: The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.
Authors: Duxin Sun; Hans Lennernas; Lynda S Welage; Jeffery L Barnett; Christopher P Landowski; David Foster; David Fleisher; Kyung-Dall Lee; Gordon L Amidon Journal: Pharm Res Date: 2002-10 Impact factor: 4.200
Authors: Zuo-Hui Shao; Terry L Vanden Hoek; Yimin Qin; Lance B Becker; Paul T Schumacker; Chang-Qing Li; Lucy Dey; Eugene Barth; Howard Halpern; Gerald M Rosen; Chun-Su Yuan Journal: Am J Physiol Heart Circ Physiol Date: 2002-03 Impact factor: 4.733